Restraint stress affects circulating NUCB2/nesfatin-1 and phoenixin levels in male rats

The two peptides phoenixin and nesfatin-1 are colocalized in hypothalamic nuclei involved in the mediation of food intake and behavior. Phoenixin stimulates food intake and is anxiolytic, while nesfatin-1 is an anorexigenic peptide shown to increase anxiety and anhedonia. Interestingly, central activation of both peptides can be stimulated by restraint stress giving rise to a role in the mediation of stress. Thus, the aim of the study was to test whether also peripheral circulating levels of NUCB2/nesfatin-1 and phoenixin are altered by restraint stress. Male ad libitum fed Sprague Dawley rats equipped with a chronic intravenous catheter were subjected to restraint stress and plasma levels of NUCB2/nesfatin-1, phoenixin and cortisol were measured over a period of 240 min and compared to levels of freely moving rats. Peripheral cortisol levels were significantly increased in restrained rats at 30, 60, 120 and 240 min compared to controls (p < 0.05). In contrast, restraint stress decreased plasma phoenixin levels at 15 min compared to unstressed conditions (0.8-fold, p < 0.05). Circulating NUCB2/nesfatin-1 levels were increased only at 240 min in restrained rats compared to those in unstressed controls (1.3-fold, p < 0.05). In addition, circulating NUCB2/nesfatin-1 levels correlated positively with phoenixin levels (r = 0.378, p < 0.001), while neither phoenixin nor nesfatin-1 were associated with cortisol levels (r = 0.0275, and r=-0.143, p> 0.05). These data suggest that both peptides, NUCB2/nesfatin-1 and phoenixin, are affected by restraint stress, although less pronounced than circulating cortisol.